鼻咽癌(Nasopharyngeal carcinoma, NPC)的強度調控放射治療(Intensity modulated radiation therapy, IMRT)因為是涉及在鼻咽部和顱底部位給予高輻射劑量。而且頭頸部區域的特徵在於包括組織，骨骼和空氣界面的複雜解剖結構，因此本研究的第一個目的是研究組織異質性對與IMRT治療NPC病人劑量分佈的影響。此外，耳朵是位於高劑量區附近的一個非常重要的危急器官並容易因輻射誘導產生副作用。所以本研究的第二個目的是開發一種高解析度(High resolution, HR)的假體以評估IMRT在耳朵的劑量分佈。

本研究改良測量式蒙特卡羅(Measurement-based Monte Carlo, MBMC)方法。MBMC研究方法的主要內容包括：(1) 利用BEAMnrc模擬Varian 21EX直線加速器治療機頭的X光束傳輸，(2)以DOSXYZnrc模擬患者劑量和(3)透過電子成像裝置(electronic portal imaging device, EPID)，用於測量IMRT治療時輻 射經過不同權重加權後的不均勻通量分佈圖。本研究所使用之設備為童綜合醫 院放射腫瘤科所有的Varian 21EX直線加速器，EPID型號為 aS1000。

研究期間共收集十位執行IMRT治療治畫的NPC病患進行評估，通過Eclipse 計劃系統中的非均向解析演算法(Anisotropic Analytical Algorithm, AAA)和 MBMC方法計算得到的劑量分佈比較，評估因組織不均勻性對劑量分布的影響。

為了進一步評估高劑量區周圍較小的危急器官對於劑量的反應，在十位NPC患者中挑選三位以及一位額外的顱底腫瘤病患，以MATLAB(R2010a版本)設計HR假體進行MBMC模擬。

以電腦斷層(computed tomography, CT)在病人頭頸部和顱底區域分別取得3毫米和1毫米的影像。再採用MATLAB中的imresize功能將影像進行雙三次插值演算法縮放，將假體的像素大小在顱底區修正為0.05×0.05×0.1立方厘米，頭部其他部分則為0.05×0.05×0.3立方厘米。

以 MBMC 模擬十位鼻咽癌患者IMRT 治療計畫的比較結果顯示MBMC 都略低於AAA，在PTV1 接受95％以上處方劑量的體積(VPTV95)，MBMC 和AAA計算結果分別為98.7％以及99.0％，在PTV1(D95％) MBMC 和AAA 計算結果分別為6832cGy 以及6895cGy。另一方面，在頭頸部治療應注意的危急器官，包括：視神經、水晶體、眼球、脊髓、顳下頜關節、腮腺和中耳等，MBMC 模擬結果和AAA 比較，上述的器官會得到更高的劑量分佈。MBMC 和 AAA 平均劑量之間的差異指出，治療時應再確認危急器官的劑量，以避免嚴重的併發症。

對小體積危急器官(體積<1立方厘米)以HR-MBMC模擬三位鼻咽癌患者的結果顯示，在PTV1平均D95％的HR-MBMC和AAA計算結果分別為6763cGy以及6847.1cGy。第八對顱神經，半規管，耳蝸的平均劑量，與AAA比較 HRMBMC 增加了287.5 cGy。模擬顱底腫瘤病患的結果也顯示耳朵的劑量HRMBMC比AAA高。HR-MBMC預測平均劑量對右側第8對腦神經，右側耳蝸以及右半規管與AAA相比分別為751.5 cGy、732.2 cGy，532.5 cGy、468.2 cGy以及870.7 cGy、 817.0 cGy。這說明HR-MBMC在顱底高劑量梯度區域中，作為分析小體積危急器官劑量分布工具的潛力。

MBMC 劑量模擬方法可以作為用於IMRT 治療範圍內具有複雜的組織成分和小體積的危急器官劑量評估參考，因為它利用EPID 可以測量非常精細的通量分佈圖。而HR-MBMC 方法則非常適合於小體積的器官，如耳朵劑量分佈的詳細評估。

Intensity modulated radiation therapy (IMRT) of nasopharyngeal cancer (NPC) involves delivering a high radiation dose to the nasopharynx, and parts of the skull base. As the head and neck region is characterized by complex anatomical structures that involve tissue, bone, and air interfaces, the first objective of this study was to study the effects of tissue heterogeneity on dose distribution in NPC patients treated with IMRT. Moreover, the ears are a very small critical organ located near the high dose area and are prone to radiation-induced toxicity. The second objective of this study, therefore, was to develop a high-resolution (HR) voxel phantom to evaluate the dose distribution of the auditory apparatus during IMRT.

The measurement-based Monte Carlo (MBMC) method was adopted for the study. The major components of the MBMC technique involves (1) the BEAMnrc code for beam transport through the treatment head of a Varian 21 EX linear accelerator, (2) the DOSXYZnrc code for patient dose simulation and (3) an electronic portal imaging device (EPID) for measuring the efficiency map which describes non-uniform fluence distribution of the IMRT treatment beam. Beam parameters and the aS1000 EPID at Tungs’ MetroHarbor hospital were commissioned for this study.

Ten NPC IMRT plans were evaluated for dose effect due to tissue heterogeneity by comparing dose distributions calculated with Eclipse plans and those obtained from the Measurement-based Monte Carlo (MBMC) method. The Eclipse plans were based on the anisotropic analytical algorithm (AAA).

For further evaluation of dose effect to small critical structures, MBMC simulations using HR phantoms (HR-MBMC) were applied to the IMRT treatment plans of three of the ten NPC patients and an additional skull base tumor. In-house MATLAB (R2010a) program was developed to create the HR voxel phantoms.

CT slices 3mm in thickness in the patient’s head and neck region and 1 mm in the skull base area were obtained. The CT images were rescaled using bicubic interpolation of the 'imresize' function in MATLAB. The voxel size of the HR phantoms was 0.05 x 0.05 x 0.1 cm3 in the skull base area and 0.05 x 0.05 x 0.3 cm3 for other parts of the phantoms.

MBMC simulation on 10 NPC patients revealed that in PTV1 the mean value of the volume receiving at least 95% of the prescribed dose (VPTV95), was slightly lower for MBMC (98.7%) than that for AAA (99.0%). The dose to 95% of PTV1 (D95%) also showed lower mean dose for MBMC (6832 cGy)
when compared with AAA (6895 cGy). On the other hand, MBMC simulation predicted a higher dose distribution to the optic nerves, lens, eyeball, spinal cord, temporomandibular joints, parotid glands, and middle ears than AAA. The difference in the mean doses between MBMC and AAA suggests that critical organ doses should be confirmed in order to avoid serious complication from overdose.

HR-MBMC simulation of three NPC patients revealed that in PTV1 the mean D95% for HR-MBMC (6763.3 cGy) was less than that for AAA (6847.1 cGy). Small volume organs (volume < 1 cm3) such as the eighth cranial nerve, semicircular canal, and cochlea showed a mean dose increase of 287.5 cGy when compared with AAA. HR phantom simulation of the skull base tumor also showed higher dose to the ear structures than AAA. The mean doses predicted by the HR-MBMC for the right 8th cranial nerve, right cochlea, and right semicircular canal compared with AAA were 751.5 cGy vs. 732.2 cGy, 532.5 cGy vs.468.2 cGy, and 870.7 cGy vs 817.0 cGy, respectively. It suggests that HR-MBMC has the potential to assist in detailed dose analysis for small critical organs (<1 cm3) in high dose gradient skull base area.

The MBMC dose simulation method can serve as a good dose evaluation reference for IMRT plans having complex tissue composition and small critical structures since it applies EPID measured efficiency maps with very fine spatial resolution. The HR-MBMC method is well suitable for detailed evaluation of dose distribution for small volume organs such as the ears.

1. Aljarrah K., Sharp G.C., Neicu T., Jiang S.B. Determination of the initial beam parameters in Monte Carlo linac simulation. Med. Phys. 33(4):850 – 858 (2006).

2. Al-Sarraf M., LeBlanc M., GiriP.G., FuK. K., Cooper J., Vuong T., Forastiere A.A., Adams G., Sakr W.A., Schuller D.E., Ensley J.F. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 16(4):1310-1317(1998).

3. Andreo P. Monte Carlo techniques in medical radiation physics. Phys Med Biol 36(7):861-920 (1991).

4. Benedict S.H.,Yenice K.M., Followill D., Galvin J.M. Hinson W., Kavanagh B., Keall P., Lovelock M., Meeks S., et al. Stereotactic body radiation therapy:The report of AAPM Task Group 101. Med Phys 37(8):4078 – 4101(2010).

5. Bentzen S.M., Constine L.S., Deasy J.O., Eisbruch A., Jackson A., Marks L. B.,Ten Haken R. K., Yorke E. D. Quantitative Analyses of normal tissue effects in the clinic (QUANTEC): An introduction to the scientific issues. Int
J Radiation Oncol Biol Phys 76(3):S3–S9 (2010).

6. Bhandare N., Jackson A., Eisbruch A., Pan C.C., Flickinger J.C., Antonelli P., Mendenhall W.M. Radiation therapy and hearing loss. Int J Radiat Oncol Biol Phys 76(3):S50 - S57 (2010).

7. Boudreau C., Heath E., Seuntjens J., Ballivy O., Parker W. IMRT head and neck treatment planning with a commercially available Monte Carlo based planning system. Phys Med Biol 50:879–890 (2005).

8. Bragg, C.M.,Wingate, K.,Conway,J.Clinical implications of the anisotropic analytical algorithm for IMRT treatment planning and verification. Radiother Oncol 86:276–284 (2008).

9. Brennan B. Nasopharyngeal carcinoma. Orphanet J Rare Dis 1:23 (2006).

10. Cancer registry annual report. 2010. Bureau of Health promotion, Department of Health, The executive Yuan, Taiwan, Republic of China (2013).

11. Chan A.T.C., Teo P.M.L., Huang D.P. Pathogenesis and Treatment of Nasopharyngeal Carcinoma. Semin Oncol 31:794-801 (2004).

12. Chan S.H., Ng W.T., Kam K.L., Lee M.C., Choi C.W., Yau T.K., Lee A.W., Chow S.K. Sensorineural hearing loss after treatment of nasopharyngeal carcinoma: a longitudinal analysis. Int J Radiat Oncol Biol Phys 73(5):1335-1342 (2009).

13. Chao K.S.C., Mohan R., Marinetti T.D., Dong L. Chapter 10 Intensity - Modulated Radiation Treatment Techniques and Clinical Applications Nasopharynx. In Perez and Brady's Principles and Practice of Radiation Oncology, 6th ed., eds. Halperin E.C., Wazer D.E., Perez C.A., Brady L.W.
Lippincott Williams & Wilkins, Philadelphia, PA 19103 USA. 221-246 (2013).

14. Chen W.C., Jackson A., Budnick A.S., Pfister D.G., Kraus D.H., Hunt M.A., Stambuk H., Levegrun S., Wolden S.L. Sensorineural hearing loss in combined modality treatment of nasopharyngeal carcinoma. Cancer 106(4): 820-829 (2006).

15. Chetty I.J., Curran B., Cygler J.E., DeMarco J.J., Ezzell G., Faddegon B.A., et al. Report of the AAPM Task Group No. 105: Issues associated with clinical implementation of Monte Carlo-based photon and electron external beam treatment planning. Med Phys 34(12):4818-4863 (2007).

16. Cheung K.Y. Intensity modulated radiotherapy: advantages, limitations and future developments Biomed Imaging Interv J 2(1): e19 (2006).

17. Chow J.C.L., Jiang R., Amir M. Owrangi A.M. Dosimetry of small bone joint calculated by the analytical anisotropic algorithm: a Monte Carlo evaluation using the EGSnrc. J Appl Clin Med Phys 15(1):262-273 (2014).

18. Chung H., Jin H., Palta J., Suh T.S., Kim S. Dose variations with varying calculation grid size in head and neck IMRT. Phys Med Biol 51: 4841 – 4856 (2006)
19. Da Silva A.A., Cebim M.A., Davolos M.R. Excitation mechanisms and effects of dopant concentration in Gd2O2S:Tb3+ phosphor. J Lumin 128 : 1165–1168 (2008).

20. Das I.J., Cao M., Cheng C.W., Misic V., Scheuring K., Schüle E., Johnstone P.A.S. A quality assurance phantom for electronic portal imaging devices. J Appl Clin Med Phys 12(2):391-403 (2011).

21. Depuydt T., Van Esch A., Huyskens D.P. A quantitative evaluation of IMRT dose distributions: refinement and clinical assessment of the gamma evaluation. Radiother Oncol 62:309–319 (2002).

22. De Smedt B., Vanderstraeten B., Reynaert N., De Neve N., Thierens H. Investigation of geometrical and scoring grid resolution for Monte Carlodose calculations for IMRT. Phys Med Biol 50:4005–4019 (2005).

23. Derenzo S.E., Weber M.J., Bourret-Courchesne E., Klintenberg M.K. The quest for the ideal inorganic scintillator. Nucl Instrum Meth A 505 : 111–117 (2003).

24. Deruty, E., How the ear works. Sound on Sound, March 2011. Available from: http://www.soundonsound.com/
25. Downes P., Spezi E. Simulating oblique incident irradiation using the BEAMnrc Monte Carlo code. Phys Med Biol 54: N93–N100 (2009).

26. Edge S.B., Byrd D.R., Compton C.C., Fritz A.G., Greene F.L., Trotti III, A. Pharynx. AJCC manual for staging of cancer. 7th ed. American joint committee on cancer (AJCC). Springer-Verlag, New York, NY. 41 - 49 (2010).

27. Elbalaa Z.A.K., Foulquier J.N., Orthuon A., Elbalaa H., Touboul E. Role of the frame cycle time in portal dose imaging using an aS500-II EPID. Phys Medica 25(3):148-153 (2009).

28. Fidanzio A. , Cilla S. , Greco F. , Gargiulo L. , Azario L., Sabatino D., Piermattei A. Generalized EPID calibration for in vivo transit dosimetry. Phys Medica 27(1):30-38 (2011).

29. Fletcher G.H., Million R.M. Malignant tumors of the nasopharynx, Am J Roentgenol 93:44-55 (1965).

30. Gagne I.M., Zavgorodni S. Evaluation of the analytical anisotropic algorithm in an extreme water–lung interface phantom using Monte Carlo dose calculations. J Appl Clin Med Phys 8(1):33-46 (2007).

31. Greer P.B., Popescu C.C., Dosimetric properties of an amorphous silicon electronic portal imaging device for verification of dynamic intensity modulated radiation therapy. Med Phys 30:1618–1627 (2003).

32. Herman M.G., Balter J.M., Jaffray D.A., McGee K. P. Munro P., Shlomo Shalev S., Van Herk M. Wong J.W. Clinical use of electronic portal imaging: Report of AAPM Radiation Therapy Committee Task Group 58. Med Phys 28(5):712-737(2001).

33. Honore H.B., Bentzen S. M., Møller K., Grau C. Sensorineural hearing loss after radiotherapy for nasopharyngeal carcinoma: individualized risk
estimation. Radiother OncoI 65(1):9-16 (2002).

34. International Commission on Radiation Units and Measurements. Prescribing, recording, and reporting photon-beam intensity-modulated radiation therapy (IMRT). ICRU Report 83. J ICRU 10:1–106 (2010).

35. Jang S. Y., Liu H.H., Mohan R. Underestimation of low-dose radiation in treatment planning of intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 71(5):1537–1546 (2008).

36. Kawrakow I., Fippel M., Friedrich K. 3D Electron Dose Calculation using a Voxel based Monte Carlo Algorithm (VMC). Med Phys 23:445 – 457 (1996).

37. Kawrakow I., Rogers D.W.O. The EGSnrc Code System: Monte Carlo Simulation of Electron and Photon Transport. NRCC report PIRS-701 (2003).

38. Kawrakow, I., Rogers D.W.O. Walters B.R.B. Large efficiency improvements in BEAMnrc using directional bremsstrahlung splitting. Med Phys 31(10):2883 – 2898 (2004).

39. Kawrakow I., Walters B. R. B. Efficient photon beam dose calculations using DOSXYZnrc with BEAMnrc. Med Phys 33(8):3046 – 3056 (2006).

40. Keall P. J., Siebers J.V., Libby B., Mohan R., Determining the incident electron fluence for Monte Carlo-based photon treatment planning using a standard measured data set. Med. Phys. 30(4):574 – 582 (2003).

41. Kirkby C., Sloboda R. Comprehensive Monte Carlo calculation of the point spread function for a commercial a-Si EPID. Med Phys 32(4):1115 – 1127 (2005).

42. Kwong D.L., Wei W.I., Sham J.S, Ho W.K., Yuen P.W., Chua D.T., Au D.K., Wu P.M., Choy D.T..Sensorineural hearing loss in patients treated for nasopharyngeal carcinoma: a prospective study of the effect of radiation and cisplatin treatment. Int J Radiat Oncol Biol Phys 36(2):281-289 (1996).

43. Lam K.S., Tse V.K., Wang C., Yeung R.T., Ma J.T., Ho J.H. Early effects of cranial irradiation on hypothalamic pituitary function. J Clin Endocrinol Metab 64(3):418–424 (1987).

44. Lee A.W.N., Ng S.H., Ho J.H.C., Tse V.K.C., Poon Y.F., Tse C.C.H., Au G.K.H., Lau W.H., Loo W.W.L. Clinical diagnosis of late temporal lobe necrosis following radiation therapy for nasopharyngeal carcinoma. Cancer 61(8):1535–1542 (1988).

45. Lee A.W.N. , Law S.C. , Ng S.H., Chan D.K., Poon Y.F., Foo W., Tung S.Y., Cheung F.K., Ho J.H. Retrospective analysis of nasopharyngeal carcinoma treated during 1976–1985: Late complications following megavoltage irradiation. Br J Radiol 65(778):918–928 (1992).

46. Lee C.C., Huang T.T., Lee M.S., Su Y.C., Chou P., Hsiao S.H., Chiou W.Y., Lin H.Y., Chien S.H., Hung S.K. Survival rate in nasopharyngeal carcinoma improved by high caseload volume: a nationwide population based study in Taiwan. Radiat Oncol 11(6):92 (2011), Available from:
http://www.ro-journal.com/content/6/1/92

47. Lee N., Xia P., Quivey J.M., Sultanem K., Poon I., Akazawa C., Akazawa P., Weinberg V., Fu K.K. Intensity modulated radiotherapy in the treatment of nasopharyngeal carcinoma: An update of the UCSF experience. Int J Radiat Oncol Biol Phys 53(1):12–22 (2002).

48. Lee N., Harris J., Garden A.S., Straube W., Glisson B., Xia P., Bosch W., Morrison W.H., Quivey J., Thorstad W., Jones C., Ang K.K. Intensity modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma: Radiation Therapy Oncology Group Phase II Trial 0225. J Clin Oncol 27:3684-3690 (2009).

49. Leibel S.A., Kutcher G.J., Harrison L.B., Fass D.E., Burman C.M., Hunt M.A., Mohan R., Brewster L.J., Ling C.C., Fuks Z.Y. Improved dose distributions for 3D conformal boost treatments in carcinoma of the nasopharynx. Int J Radiat Oncol Biol Phys 20:823–833 (1991).

50. Lin M.H. An on-line patient dose verification system for IMRT. National Tsing Hua University Masters thesis (2005).
51. Lin M.H., Chao T.C., Lee C.C., Tung C.J., Yeh C.Y., Hong J.H. Measurement- based Monte Carlo dose calculation system for IMRT pretreatment and on-line transit dose verifications. Med Phys 36(4):1167– 1175 (2009).

52. Lin M.H., Chao T.C., Lee C.C., Chang J.T.C., Tung C.J. Tissue classifications in Monte Carlo simulations of patient dose for photon beam tumor treatments. Nuclear Instruments and Methods in Physics Research A 619:393–396 (2010).

53. Lin H., Huang S., Deng X., Zhu J., Chen L. Comparison of 3D anatomical dose verification and 2D phantom dose verification of IMRT/VMAT treatments for nasopharyngeal carcinoma. Radiat Oncol. 9(1):71 (2014).
Available from: http://www.ro-journal.com/content/9/1/71.

54. Lok B.H., Setton J, Ho F., Riaz N., Rao S.S., Lee N.Y. Chapter 41 Nasopharynx. In Perez and Brady’s Principles and Practice of Radiation Oncology, 6th ed., eds. Halperin E.C., Wazer D.E., Perez C.A., Brady L.W. Lippincott Williams & Wilkins, Philadelphia, PA 19103 USA. 730-760 (2013).

55. Low D.A., Harms W.B., Mutic S., Purdy J.A. A technique for the quantitative evaluation of dose distributions. Med Phys 25(5):656-661 (1998).

56. Low K.L., Toh S.T., Wee J., Fook-Chong S.M.C., Wang D.Y.
Sensorineural hearing loss after radiotherapy and chemoradiotherapy: A single, blinded, randomized study. J Clin Oncol 24(12):1904-1909 (2006).

57. Ma C.M., Mok E., Kapur A., Pawlicki T., Findley D., Brain S., Forster K., Boyer A.L. Clinical implementation of a Monte Carlo treatment planning system. Med Phys 26(10): 2133 – 2143 (1999).

58. Marks L.B. Yorke E.D., Jackson A.,Ten Haken R.K., Constine L.S., Eisbruch A. Bentzen S.M., Nam J., Deasy J.O. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys 76(3): S10-S19 (2010).

59. Milano, M.T., Usuki,K.Y., Walter,K.A., Clark,D., Schell,M.C. Stereotactic radiosurgery and hypofractionated stereotactic radiotherapy: normal tissue dose constraints of the central nervous system. Cancer Treat Rev 37: 567– 578 (2011).

60. Moller A.R. Hearing:anatomy,physiology, and disorders of the auditory system, Second Edition. Elsevier’s Science & Technology, Oxford, UK (2006).

61. Montejo M.E., Shrieve D.C., Bentz B.G., Hunt J.P., Buchman L.O., Agarwal N., Hitchcock Y.J. IMRT with simultaneous integrated boost and concurrent chemotherapy for locoregionally advanced squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 81(5): e845–e852 (2011).

62. Morin R.L. Monte Carlo simulation in the radiological sciences. CRC Press, Boca Raton, Florida, U.S.A. 1-20 (1988).

63. Mora G., Pawlick T., Maio A., Ma C.M. Effect of voxel size on Monte Carlo dose calculations for radiotherapy treatment planning. In Advanced Monte Carlo for Radiation Physics, Particle Transport Simulation and Applications
Proceedings of the Monte Carlo 2000 Conference, Lisbon, 23-26 October 2000, eds. Kling A., Barao F., Nakagawa M., Tavora L., Vaz P., Springer- Verlag Berlin Heidelberg 549-554 (2001).

64. Ng, W.T., Lee, M.C.H., Hung, W.M., Choi, C.W., Lee, K.C., Chan, O.S.H., Lee, A.W.M. Clinical outcomes and patterns of failure after intensity modulated radiotherapy for nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 79:420–428 (2011).

65. Oh Y.T., Kim C.H., Choi J.H., Kang S.H., Chun M. Sensory neural hearing loss after concurrent cisplatin and radiation therapy for nasopharyngeal carcinoma. Radiother Oncol 72(1):79-82 (2004).

66. Pacholke D.H., Amdur R.J., Schmalfuss I.M., Louis D.,Mendenhall W.M. Contouring the middle and inner ear on radiotherapy planning scans. Am J Clin Oncol 28:143–147(2005).

67. Pan C. C., Eisbruch A., Lee J. S., Snorrason R. M., Ten Haken R. K., Kileny P. R. Prospective study of inner ear radiation dose and hearing loss in head and neck cancer patients. Int J Radiat Oncol Biol Phys 61(5):1393-
1402 (2005).

68. Papanikolaou N., Battista J.J., Boyer A.L., Klein C.K.E., Mackie T.R., Sharpe M.,Van Dyk J. AAPM Report 85, tissue inhomogeneity corrections for megavoltage photon beams. Report of AAPM Radiation Therapy Committee Task Group 65, New York, AAPM (2004).

69. Parsaei H., El-Khatib E., Rajapakshe R. The use of an electronic portal imaging system to measure portal dose and portal dose profiles. Med Phys 25(10):1903 – 1909 (1998).

70. Pena J., González-Castaño D.M., Gómez F., Sánchez-Doblado F., Hartmann G.H., Automatic determination of primary electron beam parameters in Monte Carlo simulation. Med Phys 34(3): 1076 – 1084 (2007).

71. Petsuksiri J., Sermsree A., Thephamongkhol K., Keskool P., Thongyai K., Chansilpa Y., Pattaranutaporn P. Sensorineural hearing loss after concurrent chemoradiotherapy in nasopharyngeal cancer patients. Radiat
Oncol 6:19 (2011).

72. Raeside D.E. Monte Carlo Principles and Applications. Phys Med Biol 21(2):181-197(1976).

73. Robertson R. Case of epithelioma confined to the nasopharynx, Br Med J 2:1310 (1891).

74. Robinson D. Inhomogeneity correction and the analytic anisotropic algorithm. J Appl Clin Med Phys 9(2):112-122 (2008).

75. Rogers D. W. O., Faddegon B. A., Ding G. X., Ma C.M., We J., Mackie T.R. BEAM: A Monte Carlo code to simulate radiotherapy treatment units. Med Phys 22 (5):503-524 (1995).

76. Rogers D. W. O., Walters B., I. Kawrakow I. BEAMnrc Users Manual. NRCC Report PIRS-0509(A) rev L (2013).

77. Rowshanfarzad P., McCurdy B.M.C., Sabet M., Lee C., O’Connor D.J., Greer P.B. Measurement and modeling of the effect of support arm backscatter on dosimetry with a Varian EPID. Med Phys 37(5):2269- 2278 (2010).

78. Rubin P., Casarett G. Biocontinuum of the pathophysiology paradigm in ALERT - Adverse Late Effects of Cancer Treatment: Volume 1, general concepts and specific precepts. eds Rubin P., Constine L.S., Marks L.B.
Springer-Verlag Berlin Heidelberg 19-20 (2014).

79. Sabel M., Eclipse treatment planning – the basics, (2003). Available from: http://jpkc.fimmu.com/fszlx/2-14/15Treatment%20Planning%20-%20The%20Basics.pdf.

80. Sakthi, N., Keall, P., Mihaylov, I., Wu, Q., Wu, Y., Williamson, J.F., Schmidt-Ullrich, R., Siebers, J.V. Monte Carlo-based dosimetry of head-and-neck patients treated with SIB-IMRT. Int J Radiat Oncol Biol Phys 64: 968–977 (2006).

81. Seco, J., Adams, E., Bidmead, M., Partridge, M., Verhaegen, F. Head-and neck IMRT treatments assessed with a Monte Carlo dose calculation engine. Phys Med Biol 50:817–830 (2005).

82. Schmid G., Uberbacher R., Samaras T., Jappel A., Baumgartner W.D., Tschabitscher M. Mazal P.R. High-resolution numerical model of the middle and inner ear for a detailed analysis of radio frequency absorption.
Phys Med Biol 52:1771–1781(2007).

83. Sheikh-Bagheri D., Rogers, D.W.O., Carl K. Ross C.K., Seuntjens J. P. Comparison of measured and Monte Carlo calculated dose distributions from the NRC linac. Med Phys 27(10):2256-2266 (2000).

84. Sheikh-Bagheri D., Rogers, D.W.O. Monte Carlo calculation of nine megavoltage photon beam spectra using the BEAM code. Med Phys 29(3):391-402 (2002).

85. Sheikh-Bagheri D., Rogers, D.W.O. Sensitivity of megavoltage photon beam Monte Carlo simulations to electron beam and other parameters. Med Phys 29(3): 379-390 (2002).

86. Siebers J.V., Keall P.J., Nahum A.E., Mohan R. Converting absorbed dose to medium to absorbed dose to water for Monte Carlo based photon beam dose calculations. Phys Med Biol 45:983–995 (2000).

87. Siebers J.V. Monte Carlo for Radiation Therapy Dose Calculations, Monte Carlo Refresher Course, AAPM (2002). Available from:
https://www.aapm.org/meetings/02AM/pdf/8329-90831.pdf

88. Siebers J.V., Kim J.O., Ko L., Keall P.J., Mohan R. Monte Carlo computation of dosimetric amorphous silicon electronic portal images, Med Phys 31(7): 2135-2146 (2004).

89. Sievinen J, Ulmer W, Kaissl W. AAA Photon Dose Calculation Model in Eclipse. Varian RAD# 7170B. Palo Alto, CA: Varian Medical Systems (2005).

90. Sterpin, E., Tomsej, M., De Smedt, B., Reynaert N., Vynckier S. Monte Carlo evaluation of the AAA treatment planning algorithm in a heterogeneous multilayer phantom and IMRT clinical treatments for an Elekta SL25 linear accelerator. Med Phys 34(5):1665-1677 (2007).

91. Sukumar P., Padmanaban S., Jeevanandam P., Kumar S. A. S., Nagarajan V. A study on dosimetric properties of electronic portal imaging device and its use as a quality assurance tool in Volumetric Modulated Arc Therapy.
Rep Pract Oncol Radiother 16:248–255 (2011).

92. Sun Y., Yu X.L., Luo W., Lee A.W.M., Wee J.T.S., Lee N., et al. Recommendation for a contouring method and atlas of organs at risk in nasopharyngeal carcinoma patients receiving intensity-modulated radiotherapy. Radiother Oncol 110:390–397 (2014).

93. Troff T., QC of RapidArc, European Technical Support HW: Quality Check with Portal Vision Imaging. RapidArc Workshop 2012, January 27-28th 2012, Aarhus, Denmark. Available from: http://www.ra-workshop2012.dk/

94. Ulmer W., Kaissl W. The inverse problem of a Gaussian convolution and its application to the finite size of the measurement chambers /detectors in photon and proton dosimetry. Phys Med Biol 48: 707–727 (2003).

95. Ulmer W., Pyyry J., Kaissl W. A 3D photon superposition/convolution algorithm and its foundation on results of Monte Carlo calculations. Phys Med Biol 50: 1767– 1790 (2005).

96. Van Dyk J., Barnett R.B., Cygler J.E., Shragge P.C. Commissioning and quality assurance of treatment planning computers. Int J Radiat Oncol Biol Phys 26: 261–273 (1993).

97. Van Esch A., Tillikainen L., Pyykkonen J., Tenhunen M., Helminen H., Siljamäki S., Alakuijala J., Paiusco M., Iori M., Huyskens D.P. Testing of the analytical anisotropic algorithm for photon dose calculation. Med Phys
33;11:4130-4149 (2006).

98. Varian Medical System, Eclipse Algorithms Reference Guide, P/N B501813R01A, document version 1.0. (2008).

99. Verhey L.J. Intensity Modulated Radiotherapy (IMRT) with Conventional MLC. Available from: http://www.aapm.org/meetings/99AM/pdf/2780-22797.pdf

100. Waldron J, Tin M.M., Keller A.,Lum C., Japp B., Sellmann S., van Prooijen M., Gitterman L., Blend R., Payne D., Liu F.F., Warde P., Cummings B., Pintilie M., O’Sullivan B. Limitation of conventional two dimensional radiation therapy planning in nasopharyngeal carcinoma.
Radiother Oncol 68:153–161 (2003).

101. Walters B., Kawrakow I., Rogers D.W.O. DOSXYZnrc Users Manual.NRCC Report PIRS-794 rev B (2013).

102. Wang L.F., Kuo W.R., Ho K.Y., Lee K.W., Lin C.S. Hearing loss in patients with nasopharyngeal carcinoma after chemotherapy and radiation. Kaohsiung J Med Sci 19:163-169 (2003).

103. Wang S., Gardner J.K., Gordon J.J., Li W., Clews L., Greer P.B., Siebers J.V. Monte Carlo-based adaptive EPID dose kernel accounting for different field size responses of imagers. Med Phys 36(8):3582 – 3595 (2009).

104. Wong F.C.S, Ng A.W.Y., Lee V.H.F., Lui C.M.M., Yuen K.K. Sze W.K., Leung T.W., Tung S.Y. Whole field simultaneous integrated boost intensity modulated radiotherapy for patients with nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 76(1):138–145 (2010).

105. Yeh C.Y., Lee C.C., Chao T.C., Lin M.H., Lai P.A., Liu F.H.,Tung C.J. Application of the measurement-based Monte Carlo method in nasopharyngeal cancer patients for intensity modulated radiation therapy. Radiat Phys Chem 95:240–242 (2014).

106. Yeh C.Y., Tung C.J., Chao T.C.,Lin M.H., Lee C.C. A dual resolution measurement based Monte Carlo simulation technique for detailed dose analysis of small volume organs in the skull base region. Radiat Phys Chem, in press, corrected proof, available online 6 December 2013.

107. Yeh C.Y., Lee C.C., Tung C.J., Lin M.H., Chao T.C. Measurement-based Monte Carlo simulation of high definition dose evaluation for nasopharyngeal cancer patients treated by using intensity modulated radiation therapy. Radiat Meas, in press, corrected proof, available online 20 May 2014.